| Title |
Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2
|
|---|---|
| Published in |
Nature Medicine, April 2014
|
| DOI | 10.1038/nm.3516 |
| Pubmed ID | |
| Authors |
Alastair J O'Brien, James N Fullerton, Karen A Massey, Grace Auld, Gavin Sewell, Sarah James, Justine Newson, Effie Karra, Alison Winstanley, William Alazawi, Rita Garcia-Martinez, Joan Cordoba, Anna Nicolaou, Derek W Gilroy |
| Abstract |
Liver disease is one of the leading causes of death worldwide. Patients with cirrhosis display an increased predisposition to and mortality from infection due to multimodal defects in the innate immune system; however, the causative mechanism has remained elusive. We present evidence that the cyclooxygenase (COX)-derived eicosanoid prostaglandin E2 (PGE2) drives cirrhosis-associated immunosuppression. We observed elevated circulating concentrations (more than seven times as high as in healthy volunteers) of PGE2 in patients with acute decompensation of cirrhosis. Plasma from these and patients with end-stage liver disease (ESLD) suppressed macrophage proinflammatory cytokine secretion and bacterial killing in vitro in a PGE2-dependent manner via the prostanoid type E receptor-2 (EP2), effects not seen with plasma from patients with stable cirrhosis (Child-Pugh score grade A). Albumin, which reduces PGE2 bioavailability, was decreased in the serum of patients with acute decompensation or ESLD (<30 mg/dl) and appears to have a role in modulating PGE2-mediated immune dysfunction. In vivo administration of human albumin solution to these patients significantly improved the plasma-induced impairment of macrophage proinflammatory cytokine production in vitro. Two mouse models of liver injury (bile duct ligation and carbon tetrachloride) also exhibited elevated PGE2, reduced circulating albumin concentrations and EP2-mediated immunosuppression. Treatment with COX inhibitors or albumin restored immune competence and survival following infection with group B Streptococcus. Taken together, human albumin solution infusions may be used to reduce circulating PGE2 levels, attenuating immune suppression and reducing the risk of infection in patients with acutely decompensated cirrhosis or ESLD. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 33% |
| Canada | 1 | 33% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 2 | 67% |
| Members of the public | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 183 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 1% |
| Australia | 2 | 1% |
| Japan | 2 | 1% |
| France | 1 | <1% |
| Germany | 1 | <1% |
| China | 1 | <1% |
| Hungary | 1 | <1% |
| Singapore | 1 | <1% |
| Spain | 1 | <1% |
| Other | 0 | 0% |
| Unknown | 171 | 93% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 33 | 18% |
| Researcher | 32 | 17% |
| Student > Master | 16 | 9% |
| Other | 12 | 7% |
| Student > Postgraduate | 12 | 7% |
| Other | 42 | 23% |
| Unknown | 36 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 63 | 34% |
| Agricultural and Biological Sciences | 29 | 16% |
| Biochemistry, Genetics and Molecular Biology | 12 | 7% |
| Immunology and Microbiology | 12 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 3% |
| Other | 16 | 9% |
| Unknown | 46 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 16. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 March 2021.
All research outputs
#2,228,130
of 25,121,692 outputs
Outputs from Nature Medicine
#3,794
of 9,187 outputs
Outputs of similar age
#21,992
of 233,230 outputs
Outputs of similar age from Nature Medicine
#48
of 100 outputs
Altmetric has tracked 25,121,692 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 9,187 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 104.3. This one has gotten more attention than average, scoring higher than 58% of its peers.
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